Journal article
CX3CR1 Is Expressed by Prostate Epithelial Cells and Androgens Regulate the Levels of CX3CL1/Fractalkine in the Bone Marrow: Potential Role in Prostate Cancer Bone Tropism
Cancer research (Chicago, Ill.), v 68(6), pp 1715-1722
15 Mar 2008
PMID: 18339851
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
We have previously shown that the chemokine fractalkine promotes the adhesion of human prostate cancer cells to bone marrow endothelial cells as well as their migration toward human osteoblasts
in vitro
. Thus, the interaction of fractalkine with its receptor CX3CR1 could play a crucial role
in vivo
by directing circulating prostate cancer cells to the bone. We found that although CX3CR1 is minimally detectable in epithelial cells of normal prostate glands, it is overexpressed upon malignant transformation. Interestingly, osteoblasts, stromal and mesenchymal cells derived from human bone marrow aspirates express the cell-bound form of fractalkine, whereas the soluble form of the chemokine is detected in bone marrow supernatants. To investigate the mechanisms regulating the levels of soluble fractalkine in the bone marrow, we focused on androgens, which play a critical role in both prostate cancer progression and skeletal metastasis. Here, we show that dihydrotestosterone dramatically increases the cleavage of fractalkine from the plasma membrane of bone cells and its action is reversed by nilutamide—an antagonist of the androgen receptor—as well as the wide-spectrum inhibitor of matrix metalloproteases, GM6001. However, dihydrotestosterone was unable to induce fractalkine-cleavage from human bone marrow endothelial cells. Thus, androgens could promote the extravasation of CX3CR1-bearing cancer cells on a fractalkine concentration gradient, while leaving unaltered their ability to adhere to the bone marrow endothelium. In conclusion, our results indicate that CX3CR1, fractalkine, and the enzymes responsible for its cleavage might represent suitable targets for therapies aiming to counteract skeletal secondary tumors from prostate adenocarcinoma.
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Details
- Title
- CX3CR1 Is Expressed by Prostate Epithelial Cells and Androgens Regulate the Levels of CX3CL1/Fractalkine in the Bone Marrow: Potential Role in Prostate Cancer Bone Tropism
- Creators
- Whitney L Jamieson - Departments of Pharmacology and Physiology, Drexel University College of Medicine, Philadelphia, PennsylvaniaSaori Shimizu - Departments of Pharmacology and Physiology, Drexel University College of Medicine, Philadelphia, PennsylvaniaJulia A D'Ambrosio - Departments of Pharmacology and Physiology, Drexel University College of Medicine, Philadelphia, PennsylvaniaOlimpia Meucci - Departments of Pharmacology and Physiology, Drexel University College of Medicine, Philadelphia, PennsylvaniaAlessandro Fatatis - Departments of Pharmacology and Physiology, Drexel University College of Medicine, Philadelphia, Pennsylvania
- Publication Details
- Cancer research (Chicago, Ill.), v 68(6), pp 1715-1722
- Publisher
- American Association for Cancer Research (AACR)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Pharmacology and Physiology
- Web of Science ID
- WOS:000254024400015
- Scopus ID
- 2-s2.0-40949139389
- Other Identifier
- 991014878085104721
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- Web of Science research areas
- Oncology